1. Field of the Invention
The present invention relates to a ceramide-like compound having properties of the natural ceramides, and to a method for producing the same, and to a cosmetic composition containing the same as an active ingredient.
2. Related Arts
To maintain its life action, an organism needs protective barrier which prevents noxious foreign materials including microorganisms from external penetration, and counteracts the loss of body fluids such as water and blood. In case of human beings, stratum corneum, the outermost layer of the epidermis, serves as this protective barrier. The stratum corneum prevents water within the skin from excessive evaporation, and controls penetration of foreign materials.
Dead, flat-shaped cells, comeocytes filled with keratin are embedded in the lipids of the intercellular domains to form membraneous bilayers. The corneocytes and the intercellular lipids make up the so-called permeable barrier. The intercellular space of the stratum corneum is mainly composed of glycolipids, cholesterol, free fatty acids and ceramides. Among them, the ceramides play an important role in maintaining well-balanced water content which is involved in skin elasticity, appearance and barrier functions.
However, skin aging or skin damage caused by detergents which remove the lipids essential for the barrier function may disturb lipid synthesis and reduce ceramide content in the stratum comeum. Thus, cell cohesion may be weak and the stratum corneum cannot serve as protective barrier. The skin may lose elasticity. As the ceramide content decreases, transepidermal water loss, direct exposure to exterior irritation such as UV or chemicals, and peeling off of the stratum corneum may occur and thus the skin may be rough and damaged.
It has been reported that external application, such as cosmetics or pharmaceutical application, of ceramides can recover the lamella structure disturbed by skin aging or damage of the stratum corneum. Thus, stratum corneum can fully function as protective barrier.
For the purpose of external application of ceramides, efforts have been made to find natural ceramide in animals, plants and microorganisms. As a result, various animals, plants and microorganisms containing natural ceramides were discovered. However, ceramide of natural origin is scarce, and it is difficult to isolate highly pure ceramides. Thus, supplies of natural ceramides by extraction thereof increase manufacturing cost and the price of final product. In addition, natural ceramides have low solubility in various organic solvents widely used in cosmetics. That is to say, only a small quantity of ceramides can be used in cosmetics, hindering their primary effects to an insufficient level.
The present inventors have conducted extensive studies on the molecular structure of natural ceramides in order to synthesize ceramide-like compounds which are structurally similar to natural ones. Natural ceramides have two long chain alkyl groups, amides, and hydroxyl groups. Considering this structural feature, molecular design was performed to synthesize ceramide-like compounds having two long chain alkyl groups, one or more amides and hydroxyl groups.
Because skin ceramides form a stable lamella layer in the stratum corneum for their function as the skin barrier, ceramide-like compounds should be also easily delivered into the intercellular space of the stratum corneum. Under this consideration, the present inventors introduced phosphoric or sulfuric group into the ceramide-like structures. The phosphate or sulfate group enhances the penetration through the skin surface. They are removed easily by enzymes, then transformed into more stable lipophilic form.
Further, the present inventors introduced a tocopheryl group as a hydrophobic group into the ceramide-like structures in order to prevent the biological membranes from oxidation. That is to say, a tocopheryl group is introduced into the ceramide-like structures since it has an excellent compatibility in the living body and anti-oxidation, action although the unstable property of tocopherol has limited the uses of tocopherol as a cosmetic source.
Thus, the purpose of the present invention is to provide new ceramide-like compounds represented by the following Formula (I): 
wherein,
m and n, which may be the same or different, each is independently an integer from 1 to 3, , inclusive;
k and 1, which may be the same or different, each is independently an integer from 1 to 2, inclusive;
j is 0 or 1;
OA1, OA2 and OA3, which may be the same or different, each represents OH or any one of the following structures: and 
(wherein,
M, M1 and M2 represent independently alkali metals or organic base containing nitrogen, and
L represents alkaline earth metals.)
R represents a group having the following structure: 
wherein,
B is methyl group at the 5-,7- or 8- position;
m is an integer from 1 to 3, inclusive; and
D is xe2x80x94CH2xe2x80x94CH(CH3)xe2x80x94or xe2x80x94CHxe2x95x90C(CH3)xe2x80x94.
Further, other object of the present invention is to provide a method for preparing the ceramide-like compounds (I).
Also, still other object of the present invention is to provide cosmetic compositions containing the ceramide-like compounds (I) as an active ingredient.
The above and other objects and features of the present invention will be apparent to the skilled in the art from the following detailed description.
The method of preparation of the compounds (I) according to the present invention will be described in more detail.
(1) reacting primary amino alcohol with dihalo compound or monohalo epoxy compound in alcohol under an inert atmosphere, to produce secondary amino alcohol derivative represented by the Formula (II): 
wherein, j, k, l, m and n have the same structural features as defined in Formula (I), respectively;
(2) reacting the secondary amino alcohol derivative of step (1) with tocopherylsuccinic acid chloride in the presence of an alkali or organic base to produce the diamide compound;
(3) dissolving the diamide compound of step (2) in an organic solvent, and filtering off the precipitates. After evaporating off the solvent, then recrystallizing the residue in organic solvents;
(4) phosphorylating or sulfating the diamide compound obtained in step (3);
(5) neutralizing the product of step (4) with alkali or base.
In detail, the primary amino alcohol employed in step (1) include ethanolamine, 3-amino-1-propanol and 4-amino-1-butanol and the dihalo compounds employed in step (1) include 1,3-dichloro-2-propanol, 1,3-dibromo-1-propanol, 1,2-dichloroethane and 1,2-dibromoethane. The monohalo epoxy compounds include epichlorohydrin, epibromohydrin, 3,4-epoxy-1-chlorobutane, 3,4-epoxy-1-bromobutane, 4,5-epoxy-1-chloropentane, and 4,5-epoxy-1-bromopentane.
Further, the alkali catalysts employed in step (2) include potassium hydroxide, sodium hydroxide, magnesium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, magnesium oxide and calcium oxide. The organic bases include triethanolamine and pyridine. The tocopherylsuccinic acid chloride may be obtained from synthetic or natural tocopherol. It is prepared by reacting a tocopherylsuccinic acid with a chloride such as thionyl chloride. And tocopherylsuccinic acid is obtained by reacting a succinic anhydride with a tocopherol having a type such as xcex1, xcex2, xcex3, xcex4 and xcex5.
The organic solvents employed in step (3) include alcohols such as methanol, ethanol, propanol and isopropanol; halo compounds such as dichloromethane, chloroform, 1,2-dichloroethane and carbon tetrachloride; hydrocarbons such as n-hexane, cyclohexane, benzene and toluene.
The phosphorylating reagents employed in the step (4) include phosphorus oxychloride and phosphoric anhydride. The sulfating reagents include chlorosulfonic acid and sulfur trioxide.
Further, the neutralizing agents employed in the step (5) include alkali metal or alkali earth oxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, calcium oxide and magnesium oxide; basic amino acids such as lysine, arginine and histidine; ammonia or amines such as triethanol amine; cationic polymers such as polyquaternium-4, -6, -7, -10, -11 and -16; and cationic surfactants such as lauryldimethylbenzylammonium chloride and stearyldimethylbenzyl ammonium chloride.
The ceramide-like compounds (I) prepared by the above method may protect the skin from external irritations and have skin tonicity and recuperation ability. Since these compounds exhibit good affinity to the stratum corneum, they make the lamella structure denser with various lipids including cholesterol and fatty acids within the intercellular space of the stratum corneum, thus increasing the moisture retention ability. Further, the compounds once absorbed into the stratum corneum may be decomposed by enzymes to release tocopheryl group, and thus prevent the aging of biological membranes. Also, the compounds may be decomposed by enzymes to release phosphoric or sulfuric group. The decomposed compounds have lower solubility than the original compounds, and thereby can be stabilized within the lamella structure together with various lipids.
Therefore, these ceramide-like compounds of the present invention are useful as a cosmetic active ingredient. The ceramide-like compounds of the present invention may be incorporated in the epidermal composition such as cosmetic composition. The composition may contain the ceramide-like compounds in the amount of 0.001xcx9c20% by weight, preferably 0.1xcx9c10% by weight, which can be chosen depending on the formulations or the final purposes of the composition. Further, the composition containing the ceramide-like compounds of the present invention may be formulated, but not limited thereto, skin softeners, astringents, nutrient toilet water, nutrient creams, massage creams, essences, eye essences, eye creams, cleansing creams, cleansing foams, cleansing water, packs, powders and the like.
The present invention will be described in more detail by way of the following examples. However, these examples are provided for only illustration purpose and should not be construed as limiting the scope of the invention, which is properly delineated in the accompanying claims.